title: Fructose-1,6-diphosphate protects against epileptogenesis by modifying cation-chloride co-transporters in a model of amygdaloid-kindling temporal epilepticus.
abstract: Fructose-1,6-diphosphate (FDP) shifts the metabolism of glucose from glycolysis to the pentose phosphate pathway and has anticonvulsant activity in several acute seizure animal models. In the present study, we investigated the anti-epileptogenic effects of FDP in an amygdaloid-kindling seizure model, which is an animal model of the most common form of human temporal lobe epilepsy. We found that 1.0 g/kg FDP slowed seizure progression and shortened the corresponding after-discharge duration (ADD). FDP increased the number of stimulations needed to reach seizure stages 2-5 and prolonged the cumulative ADD prior to reaching stages 3-5. It also shortened staying days and cumulative ADD in stages 4-5. However, it demonstrated no significant protective effect when administered after the animals were fully kindled. In hippocampal neurons, cation-chloride co-transporters (CCCs) are suggested to play interesting roles in epilepsy by modulating γ-aminobutyric acid (GABA)ergic activity through controlling GABAA receptor-mediated reversal potential. We examined the potential link between FDP and the hippocampal expression of two main members of the CCCs: the neuron-specific K(+)-Cl(-)co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-)co-transporter 1 (NKCC1). FDP inhibited the kindling-induced downregulation of KCC2 expression and decreased NKCC1 expression during the kindling session. Taken together, our data reveal that FDP may have protective activity against epileptogenesis, from partial to generalized tonic-clonic seizures. Furthermore, our findings suggest that the FDP-induced imbalance between KCC2 and NKCC1 expression may be involved in the neuroprotective effect.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ding
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Manman
authors.initials: M
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Mei-ping
authors.initials: MP
authors.lastname: Ding
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006597:Fructose-Bisphosphatase / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D000927:Anticonvulsants; D006597:Fructose-Bisphosphatase; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters
keywords: Amygdaloid kindling; Antiepileptogenesis; Cation-chloride cotransporters; Fructose-1,6-diphosphate; γ-Aminobutyric acid